Alveolar ventilation is regulated by systems which control both respiratory skeletal muscle activity and airway smooth muscle tone. The overall objective of the proposed program is to examine respiratory skeletal and smooth muscle control at the receptor, effector and central nervous system levels. The program consists of seven projects: 1) central regulation of respiration and circulation, 2) respiratory sensation and control of breathing, 3) neuromuscular control of breathing in human infants, 4) chemical regulation of breathing during sleep and wakefulness, 5) neuromuscular control of breathing in enzyme-induced lung disease, 6) control of airway smooth muscle and its effect on breathing, 7) chest wall mechanics and regulation of respiratory muscle activity. These projects will specifically investigate: a) the interplay of neural and chemical control systems in determining respiratory skeletal muscle activity and airway smooth muscle tone in adult and infant humans and in animals, b) the effects of higher brain centers and states of consciousness on this interaction, and c) the capacity of respiratory control systems to compensate for changes in respiratory skeletal muscle strength, endurance and coordination produced by lung diseases. Basic data will be obtained on the organization and operation of the respiratory controller and its interaction with other control systems. These data will be used to develop mathematical models to provide new insights into controller function. Additionally, the studies have been designed to identify mechanisms and risk factors for respiratory failure which will be useful in devising and evaluating therapeutic interventions.